Oral drugs must pass through the lining of the digestive tract to be absorbed into the bloodstream and take effect. Certain proteins present in the cells lining the digestive tract, known as transporters, aid this process, but for many drugs, the specific transporters they utilize are unknown. This knowledge could enhance patient treatment regimens as drugs that rely on the same transporter can interfere with each other and should not be prescribed together.
Researchers from MIT, Brigham and Women’s Hospital, and Duke University have developed a new method to identify which transporters different drugs use. This strategy involves the use of tissue models and machine-learning algorithms and has already identified an interaction between a common antibiotic and a blood thinner.
The team used various tissue models and knocked down different combinations of transporters, then used machine-learning models to predict which drugs would interact with which transporters. Out of the 23 commonly used drugs tested, the researchers made nearly 2 million predictions of potential drug interactions. Amongst these predictions was the interaction between doxycycline, an antibiotic, and warfarin, a blood thinner.
To validate these predictions, data from around 50 patients who had been taking one of those three drugs when they were prescribed doxycycline was analyzed. The results confirmed that doxycycline interacts with not only warfarin, but also digoxin, levetiracetam, and tacrolimus – drugs used to treat heart failure, seizures, and rejection in organ transplant patients, respectively.
Understanding more about the transporters that help drugs pass through the digestive tract also has implications on drug development. While identifying potential interactions between existing drugs, this strategy can also be used to optimize the formulation of new drug molecules, improving absorbability and preventing interactions with other drugs.
To that end, Vivtex, a biotech company co-founded by researchers from MIT, is applying this approach to the development of new oral drug delivery systems. Better understanding of the transporters that aid drug absorption could enable drug developers to enhance the absorptive quality of new drugs, making them safer and more effective.
This innovative approach could change the way drug interactions are studied and predicted, enabling the creation of better, safer medications.
